This project will examine the significance of the findings that streptonigrin forms complexes with transition metal divalent cations, that these complexes bind to DNA, and that transition metals greatly enhance the biological activity of streptonigrin. The nature of the ternary complex will be studied by physical chemical methods such as analysis of the red shift induced in the UV-visible spectrum of streptonigrin when it interacts with DNA or synthetic polydeoxynucleotides. The effect of base composition on binding will be determined. The possibility that the binding is intercalative will be examined by measuring the sedimentation coefficient of supercoiled DNA in the presence of varying concentrations of streptonigrin and metal ion. In order to determine the biological significance of the ternary complex, the effect of streptonigrin plus metal ions on strains of Escherichia coli, including repair-defective mutants, will be investigated under various conditions. Effects on cultured mammalian cells will be sought. Activity of various enzymes of nucleic acid metabolism will be surveyed in the presence of streptonigrin with or without metal ions. Metal ions that will receive the most attention will be zinc, cadmium and manganese; but cobalt, copper, iron and nickel will be also be considered.